Center researchers report that flavopiridol -- a natural product-based compound being investigated as a cancer drug -- represents a possible new treatment for gastrointestinal stromal tumor (GIST), the most common sarcoma of the gastrointestinal tract. Because these tumors sometimes develop resistance to the current standard treatment, imatinib (Gleevec®), novel therapies are needed.
After Memorial Sloan-Kettering scientists investigating flavopiridol's effectiveness in cancer cells noted that it caused apoptosis -- or cell death -- in GIST cell lines, surgical oncologist Samuel Singer and colleagues further assessed flavopiridol's mechanism of action in GIST cells. Results, published June 1 in Cancer Research, showed that anti-apoptotic proteins were shut off in flavopiridol-treated cells within four hours. After 24 hours, these cells showed a marked decrease in KIT protein -- the receptor essential to GIST cell survival. These flavopiridol-induced effects caused significant apoptosis, while imatinib produced minimal apoptosis in GIST cells over the same period. [PubMed Abstract]
"Flavopiridol takes a different approach to disrupting KIT signaling," said Dr. Singer. "Instead of blocking activation of the KIT receptor, as imatinib does, it inhibits total KIT expression, lowering the amount of KIT protein produced. We think the resultant apoptosis is enhanced by flavopiridol's ability to block transcription of anti-apoptotic proteins." Flavopiridol may serve as an alternative to the receptor-targeted approaches used to treat GIST tumors and other KIT-dependent malignancies.
